MRI is a non invasive technique with broad diagnostic value. The technique has gained wide clinical acceptance and is of great importance in diagnostic medicine. However, despite significant technological advancements (increasing field strength and improvement in technology), applications of MRI are limited by an intrinsically low sensitivity.
Some alternatives to enhance its sensitivity have been developed which involve ex-vivo nuclear spin polarization of agents, prior to administration and consequent in-vivo MR signal measurement.
EP1544634 discloses some of said alternative techniques, comprising among others, Dynamic Nuclear Polarisation (DNP), Para Hydrogen Induced (PHI) polarisation and Polarisation Transfer (PT) from a hyperpolarised noble gas.
U.S. Pat. No. 6,466,814 describes a method of magnetic resonance investigation comprising the production of a hyperpolarised solution of a proper high T1 agent, selected from a series of possible candidates, followed by the administration of said solution to a subject.
During hyperpolarisation of a sample (particularly as regards the DNP methods), very low temperature are often required in order to have the sample polarised in a proper solid form. In this respect, it is known in the art (see e.g. US2008095713) that successful polarization levels are generally achieved by DNP technique when the sample upon freezing forms a so called “glass” form, rather than a crystallized form. It is noticed that it can happen that carboxylic organic acids are not capable of forming a glass in their pure form as such, thus requiring the addition of a glass-forming agent thereto. In this respect, commonly used glass-forming agents, such as inter alia DMSO, may pose some tolerability issues upon in-vivo injection. Even further, the addition of a glass-forming agent generally results in low concentrations with respect to the initial molecule to be hyperpolarised.
We have now found that when a carboxylic organic acid, which is not able to form by itself a glass form upon freezing, is admixed with a suitable precursor thereof, this latter actually acts as a glass-forming agent. In particular, it has been noticed that the addition of a proper precursor to the corresponding starting carboxylic acid leads to the formation of a mixture which is able to form, upon freezing, a proper glass form, suitable for DNP experiments.
Hence, according to the invention, the use of e.g. an anhydride or an ester as glass-forming agent for the corresponding acid derivative is particularly advantageous. We have further observed that said glassed mixture when contacted with an aqueous carrier can be readily transformed in to a final solution mainly containing the starting carboxylic acid in a polarised form.
For these and other advantages which may be better appreciated by the skilled person upon reading the detailed description of the invention, the present invention provides a substantial innovative contribution over the state of the art.